Mitochondrial DNA haplogroups and neurocognitive impairment during HIV infection

Todd Hulgan; David C. Samuels; William Bush; Ronald J. Ellis; Scott L. Letendre; Robert K. Heaton; Donald R. Franklin; Peter Straub; Deborah G. Murdock; David B. Clifford; Ann C. Collier; Benjamin B. Gelman; Christina M. Marra; Justin C. Mcarthur; J. Allen Mccutchan; Susan Morgello; David M. Simpson; Igor Grant; Asha R. Kallianpur

doi:10.1093/cid/civ527

Mitochondrial DNA haplogroups and neurocognitive impairment during HIV infection

Todd Hulgan, David C. Samuels, William Bush, Ronald J. Ellis, Scott L. Letendre, Robert K. Heaton, Donald R. Franklin, Peter Straub, Deborah G. Murdock, David B. Clifford, Ann C. Collier, Benjamin B. Gelman, Christina M. Marra, Justin C. Mcarthur, J. Allen Mccutchan, Susan Morgello, David M. Simpson, Igor Grant, Asha R. Kallianpur

School of Medicine

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

Background.Neurocognitive impairment (NCI) remains an important complication in persons infected with human immunodeficiency virus (HIV). Ancestry-related mitochondrial DNA (mtDNA) haplogroups have been associated with outcomes of HIV infection and combination antiretroviral therapy (CART), and with neurodegenerative diseases. We hypothesize that mtDNA haplogroups are associated with NCI in HIV-infected adults and performed a genetic association study in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. Methods.CHARTER is an observational study of ambulatory HIV-infected adults. Haplogroups were assigned using mtDNA sequence, and principal components were derived from ancestry-informative nuclear DNA variants. Outcomes were cross-sectional global deficit score (GDS) as a continuous measure, GDS impairment (GDS ≥ 0.50), and HIV-associated neurocognitive disorder (HAND) using international criteria. Multivariable models were adjusted for comorbidity status (incidental vs contributing), current CART, plasma HIV RNA, reading ability, and CD4 cell nadir. Results.Haplogroups were available from 1027 persons; median age 43 years, median CD4 nadir 178 cells/mm³, 72% on CART, and 46% with HAND. The 102 (9.9%) persons of genetically determined admixed Hispanic ancestry had more impairment by GDS or HAND than persons of European or African ancestry (P <. 001 for all). In multivariate models including persons of admixed Hispanic ancestry, those with haplogroup B had lower GDS (β = -0.34; P =. 008) and less GDS impairment (odds ratio = 0.16; 95% confidence interval,. 04,. 63; P =. 009) than other haplogroups. There were no significant haplogroup associations among persons of European or African ancestry. Conclusions.In these mostly CART-treated persons, mtDNA haplogroup B was associated with less NCI among persons of genetically determined Hispanic ancestry. mtDNA variation may represent an ancestry-specific factor influencing NCI in HIV-infected persons.

Original language	English (US)
Pages (from-to)	1476-1484
Number of pages	9
Journal	Clinical Infectious Diseases
Volume	61
Issue number	9
DOIs	https://doi.org/10.1093/cid/civ527
State	Published - Nov 1 2015

Keywords

AIDS
DNA, mitochondrial
HIV
cognitive disorders

ASJC Scopus subject areas

Microbiology (medical)
Infectious Diseases

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10.1093/cid/civ527

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Hulgan, T., Samuels, D. C., Bush, W., Ellis, R. J., Letendre, S. L., Heaton, R. K., Franklin, D. R., Straub, P., Murdock, D. G., Clifford, D. B., Collier, A. C., Gelman, B. B., Marra, C. M., Mcarthur, J. C., Mccutchan, J. A., Morgello, S., Simpson, D. M., Grant, I., & Kallianpur, A. R. (2015). Mitochondrial DNA haplogroups and neurocognitive impairment during HIV infection. Clinical Infectious Diseases, 61(9), 1476-1484. https://doi.org/10.1093/cid/civ527

Hulgan, T, Samuels, DC, Bush, W, Ellis, RJ, Letendre, SL, Heaton, RK, Franklin, DR, Straub, P, Murdock, DG, Clifford, DB, Collier, AC, Gelman, BB, Marra, CM, Mcarthur, JC, Mccutchan, JA, Morgello, S, Simpson, DM, Grant, I & Kallianpur, AR 2015, 'Mitochondrial DNA haplogroups and neurocognitive impairment during HIV infection', Clinical Infectious Diseases, vol. 61, no. 9, pp. 1476-1484. https://doi.org/10.1093/cid/civ527

@article{94bb62e48e534ae083fdf6e90977529b,

title = "Mitochondrial DNA haplogroups and neurocognitive impairment during HIV infection",

abstract = "Background.Neurocognitive impairment (NCI) remains an important complication in persons infected with human immunodeficiency virus (HIV). Ancestry-related mitochondrial DNA (mtDNA) haplogroups have been associated with outcomes of HIV infection and combination antiretroviral therapy (CART), and with neurodegenerative diseases. We hypothesize that mtDNA haplogroups are associated with NCI in HIV-infected adults and performed a genetic association study in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. Methods.CHARTER is an observational study of ambulatory HIV-infected adults. Haplogroups were assigned using mtDNA sequence, and principal components were derived from ancestry-informative nuclear DNA variants. Outcomes were cross-sectional global deficit score (GDS) as a continuous measure, GDS impairment (GDS ≥ 0.50), and HIV-associated neurocognitive disorder (HAND) using international criteria. Multivariable models were adjusted for comorbidity status (incidental vs contributing), current CART, plasma HIV RNA, reading ability, and CD4 cell nadir. Results.Haplogroups were available from 1027 persons; median age 43 years, median CD4 nadir 178 cells/mm3, 72% on CART, and 46% with HAND. The 102 (9.9%) persons of genetically determined admixed Hispanic ancestry had more impairment by GDS or HAND than persons of European or African ancestry (P <. 001 for all). In multivariate models including persons of admixed Hispanic ancestry, those with haplogroup B had lower GDS (β = -0.34; P =. 008) and less GDS impairment (odds ratio = 0.16; 95% confidence interval,. 04,. 63; P =. 009) than other haplogroups. There were no significant haplogroup associations among persons of European or African ancestry. Conclusions.In these mostly CART-treated persons, mtDNA haplogroup B was associated with less NCI among persons of genetically determined Hispanic ancestry. mtDNA variation may represent an ancestry-specific factor influencing NCI in HIV-infected persons.",

keywords = "AIDS, DNA, mitochondrial, HIV, cognitive disorders",

author = "Todd Hulgan and Samuels, {David C.} and William Bush and Ellis, {Ronald J.} and Letendre, {Scott L.} and Heaton, {Robert K.} and Franklin, {Donald R.} and Peter Straub and Murdock, {Deborah G.} and Clifford, {David B.} and Collier, {Ann C.} and Gelman, {Benjamin B.} and Marra, {Christina M.} and Mcarthur, {Justin C.} and Mccutchan, {J. Allen} and Susan Morgello and Simpson, {David M.} and Igor Grant and Kallianpur, {Asha R.}",

note = "Publisher Copyright: {\textcopyright} The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.",

year = "2015",

month = nov,

day = "1",

doi = "10.1093/cid/civ527",

language = "English (US)",

volume = "61",

pages = "1476--1484",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "9",

}

TY - JOUR

T1 - Mitochondrial DNA haplogroups and neurocognitive impairment during HIV infection

AU - Hulgan, Todd

AU - Samuels, David C.

AU - Bush, William

AU - Ellis, Ronald J.

AU - Letendre, Scott L.

AU - Heaton, Robert K.

AU - Franklin, Donald R.

AU - Straub, Peter

AU - Murdock, Deborah G.

AU - Clifford, David B.

AU - Collier, Ann C.

AU - Gelman, Benjamin B.

AU - Marra, Christina M.

AU - Mcarthur, Justin C.

AU - Mccutchan, J. Allen

AU - Morgello, Susan

AU - Simpson, David M.

AU - Grant, Igor

AU - Kallianpur, Asha R.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Background.Neurocognitive impairment (NCI) remains an important complication in persons infected with human immunodeficiency virus (HIV). Ancestry-related mitochondrial DNA (mtDNA) haplogroups have been associated with outcomes of HIV infection and combination antiretroviral therapy (CART), and with neurodegenerative diseases. We hypothesize that mtDNA haplogroups are associated with NCI in HIV-infected adults and performed a genetic association study in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. Methods.CHARTER is an observational study of ambulatory HIV-infected adults. Haplogroups were assigned using mtDNA sequence, and principal components were derived from ancestry-informative nuclear DNA variants. Outcomes were cross-sectional global deficit score (GDS) as a continuous measure, GDS impairment (GDS ≥ 0.50), and HIV-associated neurocognitive disorder (HAND) using international criteria. Multivariable models were adjusted for comorbidity status (incidental vs contributing), current CART, plasma HIV RNA, reading ability, and CD4 cell nadir. Results.Haplogroups were available from 1027 persons; median age 43 years, median CD4 nadir 178 cells/mm3, 72% on CART, and 46% with HAND. The 102 (9.9%) persons of genetically determined admixed Hispanic ancestry had more impairment by GDS or HAND than persons of European or African ancestry (P <. 001 for all). In multivariate models including persons of admixed Hispanic ancestry, those with haplogroup B had lower GDS (β = -0.34; P =. 008) and less GDS impairment (odds ratio = 0.16; 95% confidence interval,. 04,. 63; P =. 009) than other haplogroups. There were no significant haplogroup associations among persons of European or African ancestry. Conclusions.In these mostly CART-treated persons, mtDNA haplogroup B was associated with less NCI among persons of genetically determined Hispanic ancestry. mtDNA variation may represent an ancestry-specific factor influencing NCI in HIV-infected persons.

AB - Background.Neurocognitive impairment (NCI) remains an important complication in persons infected with human immunodeficiency virus (HIV). Ancestry-related mitochondrial DNA (mtDNA) haplogroups have been associated with outcomes of HIV infection and combination antiretroviral therapy (CART), and with neurodegenerative diseases. We hypothesize that mtDNA haplogroups are associated with NCI in HIV-infected adults and performed a genetic association study in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. Methods.CHARTER is an observational study of ambulatory HIV-infected adults. Haplogroups were assigned using mtDNA sequence, and principal components were derived from ancestry-informative nuclear DNA variants. Outcomes were cross-sectional global deficit score (GDS) as a continuous measure, GDS impairment (GDS ≥ 0.50), and HIV-associated neurocognitive disorder (HAND) using international criteria. Multivariable models were adjusted for comorbidity status (incidental vs contributing), current CART, plasma HIV RNA, reading ability, and CD4 cell nadir. Results.Haplogroups were available from 1027 persons; median age 43 years, median CD4 nadir 178 cells/mm3, 72% on CART, and 46% with HAND. The 102 (9.9%) persons of genetically determined admixed Hispanic ancestry had more impairment by GDS or HAND than persons of European or African ancestry (P <. 001 for all). In multivariate models including persons of admixed Hispanic ancestry, those with haplogroup B had lower GDS (β = -0.34; P =. 008) and less GDS impairment (odds ratio = 0.16; 95% confidence interval,. 04,. 63; P =. 009) than other haplogroups. There were no significant haplogroup associations among persons of European or African ancestry. Conclusions.In these mostly CART-treated persons, mtDNA haplogroup B was associated with less NCI among persons of genetically determined Hispanic ancestry. mtDNA variation may represent an ancestry-specific factor influencing NCI in HIV-infected persons.

KW - AIDS

KW - DNA, mitochondrial

KW - HIV

KW - cognitive disorders

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DO - 10.1093/cid/civ527

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SN - 1058-4838

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JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

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Mitochondrial DNA haplogroups and neurocognitive impairment during HIV infection

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